Idiopathic CD4 Lymphocytopenia: Spectrum of opportunistic infections, malignancies, and autoimmune diseases

Late onset combined immunodeficiency (LOCID) is a recently described variant of common variable immunodeficiency (CVID), involving adult patients presenting with opportunistic infections and/or low CD4+ lymphocyte counts. A 36-year-old male with unremarkable past medical history presented with fever, respiratory failure, and lymphocytopenia. He was found to havePneumocystis jirovecipneumonia (PJP), subsequently complicated by recurrent hospital-acquiredPseudomonas aeruginosapneumonia and immune reconstitution phenomena, attributed to restoration of immunoglobulin levels. Clinicians should be aware of LOCID, which could be confused with HIV infection/AIDS or idiopathic CD4 lymphocytopenia. In the English bibliography there is only one case report, where PJP was the initial presentation of CVID (that case would probably be classified as LOCID). Phenomena of immune reconstitution are described in various settings, including primary immunodeficiency, manifesting as temporary clinical and radiologic deterioration and leading to misperceptions of therapeutic failure and/or presence of alternative/additional diagnoses.

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Opportunistic Infections in Persons With Idiopathic CD4 Lymphocytopenia

Infectious Diseases in Clinical Practice ◽

10.1097/ipc.0b013e31816fd577 ◽

2008 ◽

Vol 16 (4) ◽

pp. 218-221 ◽

Cited By ~ 1

Author(s):

Simha Jagadeesh ◽

Bharti Asnani ◽

Roger E. Nieman

Keyword(s):

Opportunistic Infections ◽

Idiopathic Cd4 Lymphocytopenia

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Idiopathic Cd4+ Lymphocytopenia In Overlap Syndrome (Systemic Sclerosis With Dermatopolimyositis)

Indonesian Journal of Rheumatology ◽

10.37275/ijr.v13i1.165 ◽

2021 ◽

Vol 13 (1) ◽

pp. 486-491

Author(s):

Sumartini Dewi ◽

Tasya Aniza Yusuf ◽

Fahrizal Yanuar

Keyword(s):

Systemic Sclerosis ◽

Autoimmune Diseases ◽

Skin Rash ◽

Clinical Manifestation ◽

Lower Extremities ◽

Severe Infection ◽

Absolute Lymphocyte Count ◽

Oral Ulcers ◽

Current Medication ◽

Idiopathic Cd4 Lymphocytopenia

Background : Idiopathic CD4 T cell lymphocytopenia (ICL) is a rare syndrome with varied clinical manifestation, characterized with lymphopenia and decreased in CD4 level without HIV infection or other possible cause of immunodeficiency state. Autoimmune diseases might be a clinical manifestation of ICL. However, it is not known whether ICL triggered an autoimmune diseases, or it is a complication of said diseases. Objective : Awareness of ICL in patient with known autoimmune diseases whom admitted to the hospital for severe infection. Methods : This case report showed a 24-years old woman with prolonged fever since 4 moths ago. It was accompanied with oral ulcers, skin rash in face and trunks, and weakness of lower extremities. She was diagnosed with systemic sclerosis since 2016 and routinely came to rheumatology outpatient clinic in Hasan Sadikin Hospital but stopped coming for past 4 months since pandemic. Her current medication was only 4 mg of methylprednisolone. Results : She had high temperature (38.5 degree Celsius) and tachycardia. Physical examination revealed a single lymphadenopathy at neck. Raynaud phenomenon, calcinosis, and sclerodactyly was found in lower extremities. Dermatomyositis was diagnosed based by heliotropic skin rash. Laboratory tests showed leukopenia, absolute lymphocyte count 135.2 cell/mm3, absolute CD4 39/uL, CK level of 3296 and nonreactive anti-HIV. The patient underwent empirical antibiotic treatment, but unfortunately passed away. Conclusion : ICL is a rare case, following an infection, autoimmune diseases, or unspecified malignancy. Clinician’s awareness toward ICL could prevent fatal opportunistic infection which often happens to patients with immunodeficiency state.

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Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors

Blood ◽

10.1182/blood-2007-12-127878 ◽

2008 ◽

Vol 112 (2) ◽

pp. 287-294 ◽

Cited By ~ 132

Author(s):

Dimitrios I. Zonios ◽

Judith Falloon ◽

John E. Bennett ◽

Pamela A. Shaw ◽

Doreen Chaitt ◽

...

Keyword(s):

Prognostic Factors ◽

T Cell ◽

Natural History ◽

Opportunistic Infection ◽

T Cell Activation ◽

Cell Activation ◽

Opportunistic Infections ◽

Cd4 T Cell ◽

Cell Counts ◽

Idiopathic Cd4 Lymphocytopenia

AbstractIdiopathic CD4+ lymphocytopenia (ICL) is a rare non–HIV-related syndrome with unclear natural history and prognosis. This prospective natural history cohort study describes the clinical course, CD4 T lymphocyte kinetics, outcome, and prognostic factors of ICL. Thirty-nine patients (17 men, 22 women) 25 to 85 years old with ICL were evaluated between 1992 and 2006, and 36 were followed for a median of 49.5 months. Cryptococcal and nontuberculous mycobacterial infections were the major presenting opportunistic infections. Seven patients presented with no infection. In 32, CD4 T-cell counts remained less than 300/mm3 throughout the study period and in 7 normalized after an average of 31 months. Overall, 15 (41.6%) developed an opportunistic infection in follow-up, 5 (13.8%) of which were “AIDS-defining clinical conditions,” and 4 (11.1%) developed autoimmune diseases. Seven patients died, 4 from ICL-related opportunistic infections, within 42 months after diagnosis. Immunologic analyses revealed increased activation and turnover in CD4 but not CD8 T lymphocytes. CD8 T lymphocytopenia (< 180/mm3) and the degree of CD4 T cell activation (measured by HLA-DR expression) at presentation were associated with adverse outcome (opportunistic infection-related death; P = .003 and .02, respectively). This trial is registered at http://clinicaltrials.gov as #NCT00001319.

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FRI0440 RISK FACTORS FOR CYTOMEGALOVIRUS INFECTION IN PATIENTS WITH AUTOIMMUNE DISEASES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2693 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 818.1-818

Author(s):

D. Kobayashi ◽

Y. Wada ◽

E. Hasegawa ◽

A. Wakamatsu ◽

T. Nakatsue ◽

...

Keyword(s):

Risk Factors ◽

At Risk ◽

Autoimmune Diseases ◽

Induction Therapy ◽

Hba1c Level ◽

Opportunistic Infections ◽

Pulse Therapy ◽

Remission Induction ◽

Cmv Infection ◽

Pp65 Antigen

Background:The risk for opportunistic infections in patients with autoimmune diseases requiring intensive immunosuppressive therapy is high and cytomegalovirus (CMV) infection is one of the most common opportunistic infections. Since 2011, we have performed weekly CMV pp65 antigen testing for patients at risk of opportunistic infections owing to autoimmune diseases to ensure appropriate patient management.Objectives:To evaluate the risk factors that predict CMV infection in patients that received remission-induction therapy for autoimmune diseases.Methods:We enrolled 254 patients (93 male, 161 female) from our hospital with autoimmune disease and who received remission-induction therapy with prednisolone at a dose greater than 0.5 mg/kg/day between January 2011 and December 2018. We retrospectively analysed their clinical characteristics and laboratory data, including treatment regimens and CMV pp65 antigen test results. The presence of more than five CMV pp65 antigen-positive cells over two slides was considered a positive result. We conducted univariate and multivariate analyses to extract CMV risk factors.Results:Of the patients we evaluated, 60 suffered from systemic lupus erythematosus (SLE), 55 from anti-nucleolar cytoplasmic antibody-associated vasculitis (AAV), 31 from dermatomyositis (DM), 14 from interstitial pneumonia with anti-aminoacyl tRNA synthetase antibody, 14 from adult-onset Still’s disease (AOSD), 14 from rheumatoid arthritis (RA), 11 from mixed connective tissue disease (MCTD), 10 from Takayasu’s aortitis, and 45 suffered from other autoimmune diseases. Pulse therapy with methylprednisolone (mPSL) and immunosuppressive reagents were administered to 103 (40.6 %) and 97 (38.2 %), respectively. The median follow-up period was 61.0 days, and 66 patients became CMV pp65 antigen-positive during this period (SLE, 15; DM, 14; AAV, 9; AOSD, 8; and other, 20). Univariate analysis revealed that when compared to patients testing negative for the CMV pp65 antigen patients testing positive had lower total lymphocyte count (TLC) (825 /uL vs. 1220 /uL; p < 0.01), a lower serum albumin level (2.70 g/dL vs. 3.30 g/dL; p < 0.01), a higher HbA1c level (6.3 % vs. 5.9 %; p<0.01), and were older (66.0 vs. 59.5 year old; p < 0.01). Forty-nine of the 66 patients in the positive group received mPSL pulse therapy (p < 0.01), and 38 received immunosuppressive reagents (p < 0.01). Logistic regression analyses indicated that a higher age by decade (OR; 1.46 [95%CI 1.06 - 2.00]), a lower TLC per 100/uL (OR; 0.83 [95%CI 0.73 -0.94]), a higher HbA1c level per 1% (OR; 2.37 [95%CI 1.25-4.53]), and mPSL pulse therapy (OR; 3.92 [95%CI 1.33-11.5]) were risk factors for CMV pp65 antigen positivity.Conclusion:Higher age, lower TLC, higher HbA1c, and treatment with mPSL pulse therapy were risk factors for acquiring CMV infection, as measured by the presence of the CMV pp65 antigen, in patients receiving remission-induction therapy for autoimmune diseases. Careful monitoring of these, at risk, patients is necessary.Disclosure of Interests:None declared

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Life-Threatening Asymptomatic Incidentaloma: A Case Report of Idiopathic CD4 Lymphocytopenia and Opportunistic Infections

The American Journal of the Medical Sciences ◽

10.1097/maj.0b013e3181e5f118 ◽

2010 ◽

Vol 340 (2) ◽

pp. 158-159 ◽

Cited By ~ 3

Author(s):

Ephraim L. Tsalik ◽

Lauren Brett Jaggers

Keyword(s):

Case Report ◽

Opportunistic Infections ◽

Life Threatening ◽

Idiopathic Cd4 Lymphocytopenia

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Immunosuppressors and immunomodulators in Neurology - Part I: a guide for management of patients underimmunotherapy

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x-anp-2020-0593 ◽

2021 ◽

Vol 79 (11) ◽

pp. 1012-1025

Author(s):

Fabiano Ferreira Abrantes ◽

Marianna Pinheiro Moraes de Moraes ◽

José Marcos Vieira de Albuquerque Filho ◽

Jéssica Monique Dias Alencar ◽

Alexandre Bussinger Lopes ◽

...

Keyword(s):

Autoimmune Diseases ◽

Adverse Reactions ◽

Opportunistic Infections ◽

Treatment Plan ◽

Treatment Success ◽

Primary Prophylaxis ◽

Infectious Complications ◽

Immunomodulatory Drugs ◽

Specific Safety

ABSTRACT For patients with autoimmune diseases, the risks and benefits of immunosuppressive or immunomodulatory treatment are a matter of continual concern. Knowledge of the follow-up routine for each drug is crucial, in order to attain better outcomes and avoid new disease activity or occurrence of adverse effects. To achieve control of autoimmune diseases, immunosuppressive and immunomodulatory drugs act on different pathways of the immune response. Knowledge of the mechanisms of action of these drugs and their recommended doses, adverse reactions and risks of infection and malignancy is essential for safe treatment. Each drug has a specific safety profile, and management should be adapted for different circumstances during the treatment. Primary prophylaxis for opportunistic infections and vaccination are indispensable steps during the treatment plan, given that these prevent potential severe infectious complications. General neurologists frequently prescribe immunosuppressive and immunomodulatory drugs, and awareness of the characteristics of each drug is crucial for treatment success. Implementation of a routine before, during and after use of these drugs avoids treatment-related complications and enables superior disease control.

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Preserved MAIT cell numbers and function in idiopathic CD4 lymphocytopenia

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa782 ◽

2020 ◽

Author(s):

Ornella Sortino ◽

Joana Dias ◽

Megan Anderson ◽

Elizabeth Laidlaw ◽

Edwin Leeansyah ◽

...

Keyword(s):

T Cells ◽

Opportunistic Infections ◽

Cell Subset ◽

Cd4 T Cell ◽

Effector Functions ◽

Mait Cells ◽

Cell Counts ◽

Idiopathic Cd4 Lymphocytopenia ◽

And Function ◽

Mait Cell

Abstract Mucosal-associated invariant T (MAIT) cells constitute a subset of unconventional, MR1-restricted T-cells involved in antimicrobial responses as well as inflammatory, allergic and autoimmune diseases. Chronic infection and inflammatory disorders as well as immunodeficiencies are often associated with decline and/or dysfunction of MAIT cells. Herein, we investigate the MAIT cells in patients with idiopathic CD4 + lymphocytopenia (ICL), a syndrome characterized by consistently low CD4 T-cell counts (<300 cell/µL) in the absence of HIV infection or other known immunodeficiency, and by susceptibility to certain opportunistic infections. The numbers, phenotype and function of MAIT cells in peripheral blood were preserved in ICL patients compared to healthy controls. Furthermore, administration of IL-7 to ICL patients expanded the CD8 + MAIT cell subset, with maintained responsiveness and effector functions after IL-7 treatment. In conclusion, ICL patients maintain normal levels and function of MAIT cells preserving some antibacterial responses despite the deficiency in CD4 + T cells.

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Kv1.3 inhibitors: en route to clinical trials

10.14293/p2199-8442.1.sop-chem.pdkxfg.v1 ◽

2014 ◽

Author(s):

Stefan Tasler ◽

Tobias Dreker ◽

Ilga Krimmelbein ◽

Svetlana Hamm

Keyword(s):

T Cells ◽

Autoimmune Diseases ◽

Opportunistic Infections ◽

Clinical Biochemistry ◽

Oral Treatment ◽

Fine Tuning ◽

Promising Target ◽

High Doses ◽

Selling Point ◽

Positive Controls

The voltage-gated potassium channel Kv1.3 represents a promising target for the treatment of autoimmune diseases like multiple sclerosis, rheumatoid arthritis, uveitis and psoriasis as it is a crucial player in maintaining the activation signal within T-cells, allowing for a selective suppression of autoimmunity and thus minimizing the potential for opportunistic infections during therapy. The Lead Optimization Program for two small molecule hit classes resulted in a fine-tuning of activity, selectivity and physicochemical and PK properties. Selected representatives display highly encouraging ameliorative effects within a set of animal models relevant in the context of autoimmune diseases, comparable or even favourable over positive controls like methotrexate, betamethasone or tacrolimus. Such inhibitors showed excellent tolerability in rats upon oral treatment with high doses for up to a month, had no effect on haematology and clinical biochemistry parameters and did not affect cells of the innate immunity or naive T-cells, clearly emphasizing their unique selling point, which is a highly specific immunosuppression of autoreactive T-cells.

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